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Loss of GM-CSF-dependent instruction of alveolar macrophages in COVID-19 provides a rationale for inhaled GM-CSF treatment

Cedric Bosteels (UGent) , Karel Van Damme (UGent) , Elisabeth De Leeuw (UGent) , Jozefien Declercq (UGent) , Bastiaan Maes (UGent) , Victor Bosteels (UGent) , Levi Hoste (UGent) , Leslie Naesens (UGent) , Nincy Debeuf (UGent) , Julie Deckers (UGent) , et al.
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Abstract
GM-CSF promotes myelopoiesis and inflammation, and GM-CSF blockade is being evaluated as a treatment for COVID-19-associated hyperinflammation. Alveolar GM-CSF is, however, required for monocytes to differentiate into alveolar macrophages (AMs) that control alveolar homeostasis. By mapping cross-species AM development to clinical lung samples, we discovered that COVID-19 is marked by defective GM-CSF-dependent AM instruction and accumulation of pro-inflammatory macrophages. In a multi-center, open-label RCT in 81 non-ventilated COVID-19 patients with respiratory failure, we found that inhalation of rhu-GM-CSF did not improve mean oxygenation parameters compared with standard treatment. However, more patients on GM-CSF had a clinical response, and GM-CSF inhalation induced higher numbers of virus-specific CD8 effector lymphocytes and class-switched B cells, without exacerbating systemic hyperinflammation. This translational proof-of-concept study provides a rationale for further testing of inhaled GM-CSF as a non-invasive treatment to improve alveolar gas exchange and simultaneously boost antiviral immunity in COVID-19. This study is registered at ClinicalTrials.gov (NCT04326920) and EudraCT (2020-001254-22).
Keywords
COLONY-STIMULATING FACTOR, EPITHELIAL-CELLS, FETAL MONOCYTES, DENDRITIC, CELL, DIFFERENTIATION, LUNG, EXPRESSION, PNEUMONIA, DEVELOP, TRIAL

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MLA
Bosteels, Cedric, et al. “Loss of GM-CSF-Dependent Instruction of Alveolar Macrophages in COVID-19 Provides a Rationale for Inhaled GM-CSF Treatment.” CELL REPORTS MEDICINE, vol. 3, no. 12, Elsevier, 2022, doi:10.1016/j.xcrm.2022.100833.
APA
Bosteels, C., Van Damme, K., De Leeuw, E., Declercq, J., Maes, B., Bosteels, V., … Lambrecht, B. (2022). Loss of GM-CSF-dependent instruction of alveolar macrophages in COVID-19 provides a rationale for inhaled GM-CSF treatment. CELL REPORTS MEDICINE, 3(12). https://doi.org/10.1016/j.xcrm.2022.100833
Chicago author-date
Bosteels, Cedric, Karel Van Damme, Elisabeth De Leeuw, Jozefien Declercq, Bastiaan Maes, Victor Bosteels, Levi Hoste, et al. 2022. “Loss of GM-CSF-Dependent Instruction of Alveolar Macrophages in COVID-19 Provides a Rationale for Inhaled GM-CSF Treatment.” CELL REPORTS MEDICINE 3 (12). https://doi.org/10.1016/j.xcrm.2022.100833.
Chicago author-date (all authors)
Bosteels, Cedric, Karel Van Damme, Elisabeth De Leeuw, Jozefien Declercq, Bastiaan Maes, Victor Bosteels, Levi Hoste, Leslie Naesens, Nincy Debeuf, Julie Deckers, Basiel Cole, Marion Pardons, Daniela Weiskopf, Alessandro Sette, Yannick Vande Weygaerde, Thomas Malfait, Stefaan J. Vandecasteele, Ingel K. Demedts, Hans Slabbynck, Sabine Allard, Pieter Depuydt, Eva Van Braeckel, Jozefien De Clercq, Liesbet Martens, Sam Dupont, Ruth Seurinck, Niels Vandamme, Filomeen Haerynck, Debasish F. Roychowdhury, Linos Vandekerckhove, Martin Guilliams, Simon Tavernier, and Bart Lambrecht. 2022. “Loss of GM-CSF-Dependent Instruction of Alveolar Macrophages in COVID-19 Provides a Rationale for Inhaled GM-CSF Treatment.” CELL REPORTS MEDICINE 3 (12). doi:10.1016/j.xcrm.2022.100833.
Vancouver
1.
Bosteels C, Van Damme K, De Leeuw E, Declercq J, Maes B, Bosteels V, et al. Loss of GM-CSF-dependent instruction of alveolar macrophages in COVID-19 provides a rationale for inhaled GM-CSF treatment. CELL REPORTS MEDICINE. 2022;3(12).
IEEE
[1]
C. Bosteels et al., “Loss of GM-CSF-dependent instruction of alveolar macrophages in COVID-19 provides a rationale for inhaled GM-CSF treatment,” CELL REPORTS MEDICINE, vol. 3, no. 12, 2022.
@article{01GS54ZR612NJP21RB7F63AQHA,
  abstract     = {{GM-CSF promotes myelopoiesis and inflammation, and GM-CSF blockade is being evaluated as a treatment for COVID-19-associated hyperinflammation. Alveolar GM-CSF is, however, required for monocytes to differentiate into alveolar macrophages (AMs) that control alveolar homeostasis. By mapping cross-species AM development to clinical lung samples, we discovered that COVID-19 is marked by defective GM-CSF-dependent AM instruction and accumulation of pro-inflammatory macrophages. In a multi-center, open-label RCT in 81 non-ventilated COVID-19 patients with respiratory failure, we found that inhalation of rhu-GM-CSF did not improve mean oxygenation parameters compared with standard treatment. However, more patients on GM-CSF had a clinical response, and GM-CSF inhalation induced higher numbers of virus-specific CD8 effector lymphocytes and class-switched B cells, without exacerbating systemic hyperinflammation. This translational proof-of-concept study provides a rationale for further testing of inhaled GM-CSF as a non-invasive treatment to improve alveolar gas exchange and simultaneously boost antiviral immunity in COVID-19. This study is registered at ClinicalTrials.gov (NCT04326920) and EudraCT (2020-001254-22).}},
  articleno    = {{100833}},
  author       = {{Bosteels, Cedric and Van Damme, Karel and De Leeuw, Elisabeth and Declercq, Jozefien and Maes, Bastiaan and Bosteels, Victor and Hoste, Levi and Naesens, Leslie and Debeuf, Nincy and Deckers, Julie and Cole, Basiel and Pardons, Marion and  Weiskopf, Daniela and  Sette, Alessandro and Vande Weygaerde, Yannick and Malfait, Thomas and  Vandecasteele, Stefaan J. and  Demedts, Ingel K. and  Slabbynck, Hans and  Allard, Sabine and Depuydt, Pieter and Van Braeckel, Eva and De Clercq, Jozefien and Martens, Liesbet and Dupont, Sam and Seurinck, Ruth and Vandamme, Niels and Haerynck, Filomeen and  Roychowdhury, Debasish F. and Vandekerckhove, Linos and Guilliams, Martin and Tavernier, Simon and Lambrecht, Bart}},
  issn         = {{2666-3791}},
  journal      = {{CELL REPORTS MEDICINE}},
  keywords     = {{COLONY-STIMULATING FACTOR,EPITHELIAL-CELLS,FETAL MONOCYTES,DENDRITIC,CELL,DIFFERENTIATION,LUNG,EXPRESSION,PNEUMONIA,DEVELOP,TRIAL}},
  language     = {{eng}},
  number       = {{12}},
  pages        = {{25}},
  publisher    = {{Elsevier}},
  title        = {{Loss of GM-CSF-dependent instruction of alveolar macrophages in COVID-19 provides a rationale for inhaled GM-CSF treatment}},
  url          = {{http://doi.org/10.1016/j.xcrm.2022.100833}},
  volume       = {{3}},
  year         = {{2022}},
}

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